Canadian Macromolecular Crystallography Facility

News and Updates

Over the past years, the CMCF has invested in over 100 Uni-Pucks to facilitate introduction of efficient automated methods that allow Remote Control, with significant time and cost-savings from reduced travel. The equipment facilitates bringing new User Groups into the life of the facility and is used heavily for the annual CLS Mx Data Collection School. We hope to continue having loaner Uni-Pucks and tools available for those who may occasionally need extra equipment, and to support the introduction of new research groups.

At the moment, the CMCF has no more loaner Uni-Pucks available. If your group has been considering the purchase of dedicated Uni-Pucks and tools, it would be an ideal time for CLS Uni-Pucks that are being replaced to be returned to the CMCF for the benefit of the community.

Please feel free to contact us for advice on purchasing Uni-Pucks or other equipment. There is information along with links to suppliers on the CMCF Samples & Automounters page. We hope that the availability of the loaner equipment has served CMCF Users well and we hope to be able to continue this tradition!

The CLS will be in shut-down mode and closed during the last week of December until after New Year's Day. We wish you a Merry Christmas, Happy Holidays, and look forward to working with you again in the New Year!

Repairs to the CLS electron gun are proceeding on track. Because we will only know conclusively if the repairs have been fully successful in mid-December, we are tentatively scheduling February beamtime. It is anticipated that most of January will be devoted to bringing the system back up, including linac, booster ring, storage ring and beamlines. CMCF is now reserving anticipated February shifts using normal procedures, based on Shift Requests through the CLS User Portal for Peer-Reviewed Projects. Commercial usage will be arranged through your Industrial Contact as usual. We thank everyone for their patience during this period and look forward to working with you in the New Year.

On June 27, the facility's electron source failed, resulting in loss of beam. Several malfunctioning components were identified in the main electron gun’s power supply. After initial repairs, CLS staff members determined that the power supply’s transformer needed to be replaced. We regret the impact this outage will have on affected projects, and CLS staff are doing everything possible to resolve the problem. In order to complete the repairs, the CLS has had to cancel user shifts until January 2019.

On June 27, the facility's electron source failed, resulting in loss of beam. Several malfunctioning components were identified in the main electron gun’s power supply. After initial repairs, CLS staff members determined that the power supply’s transformer needed to be replaced. We regret the impact this outage will have on affected projects, and CLS staff are doing everything possible to resolve the problem. In order to complete the repairs, the CLS has had to cancel user shifts until November. Additionally, the CLS will not be opening the August call for new proposals.

LPS is a major bacterial component recognized by the immune system, eliciting an inflammatory response followed by a state of immune tolerance. Acyloxyacyl hydrolase detoxifies LPS to re-establish sensitivity for subsequent infections. The structures described in this work address the questions of LPS recognition and selectivity toward acyl chains. Here, human acyloxyacyl hydrolase is shown with myristic, lauric and palmitic acids hidden deep within a hydrophobic pocket. PDB ID 5W78.

Protein O-fucosyltransferase 1 (POFUT1) fucosylates cell-surface and secreted glycoproteins including Notch, which is critical during cellular development. Aberrations in this pathway may be linked to generalized Dowling-Degos disease. POFUT1 may also be a novel therapeutic target for cardiac disease and cancer. In this structure obtained from Mail-In data, mouse POFUT1 is in complex with mouse Notch1 EGF26 and GDP. PDB ID 5KY4.

Coronavirus spike protein mediates receptor binding and fusion of viral and host cell membranes. Results from this project provide a model for coronavirus adaptation to environmental changes based on the use of three extended loops for receptor binding, with such loop regions being inherently accommodating to mutational changes. Given their wide host range and zoonotic transmission to humans, coronavirus provides an important model for studying RNA viruses and emergence of new viral threats. PDB ID 6ATK.

Macrolides are a class of antibiotic used to treat respiratory tract, skin, and soft tissue infections especially in patients sensitive to β-lactam antibiotics. But, bacteria can inactivate them with macrolide phosphotransferase enzymes. In this structure, azithromycin is bound near the active site of macrolide 2’-phosphotransferase type I, with guanosine. The large antibiotic binding pocket accommodates a variety of macrolides, explaining the broad-spectrum resistance conferred by these enzymes. PDB ID 5IGI.

Benzo[a]pyrene (BP) is a frequently-encountered carcinogen that generates a bulky DNA adduct. DNA polymerase kappa is the only known polymerase that can bypass the adduct accurately and protect cells from genotoxic effects. In this Mail-In project, the authors compare binding of normal DNA with BP-adducted DNA to unravel the unique mechanism for accurate replication. PDB ID 4U7C.

Applications are open for the 8th Annual CLS Mx Data Collection School, being held June 4 - 8, 2018. This is an intensive 5-day hands-on data collection school intended to equip participants to effectively collect crystal diffraction data at the synchrotron as well as make use of the CMCF beamlines remotely. Attendance is limited so early application is encouraged. Application deadline is April 10. See the School webpage for more information.

Recently the CLS has transitioned to a new User Portal with additional features that you should be aware of. You can log in at https://user-portal.lightsource.ca using the same username and password that you use to access the CLS training system. If you have any trouble accessing the new User Portal, or using any of the new features, please email the USO at clsuo@lightsource.ca or call 306-657-3700.

You should have received an email from the Users Office with details and a link to some instructions: User Portal Help

At the start of your beamtime, you will have an Active Session available on your dashboard. When the beamline is ready, your local contact will be in touch, as usual, if you have any questions about the Sign-On process.

This year marked the 1000th protein structure identified using data collected at the CMCF, and deposited to the PDB. This image comprises one "pixel" for each of those proteins, and represents our users' contributions to research in cancer, heart disease, HIV, Parkinson's, antibiotic resistance, neurodegenerative diseases, and much, much more.

CMCF Users will notice a change in the CMCF data acquisition software, MxDC. MxDC now has additional features, including automatic customizable directory creation, improved automatic crystal centering, vector data collection and improved in-app data analysis for Mx experiments as well as XAS, EXAFS and powder diffraction. For a description of the changes and new features, please visit the MxDC page!

We are happy to announce that the first session of data collection using the newly-installed IRELEC ISARA sample changer on beamline CMCF-ID occurred on November 30, 2017. Dr. Trevor Moraes and colleagues from the University of Toronto were the first to put the new capabilities to the test during a remote data collection session. This upgrade follows on the heels of the installation of a new Pilatus detector and, together, these components allow much higher sample throughput on CMCF-ID. The new sample changer on CMCF-ID now accepts Uni-Pucks only. There is no change to the sample changer on the CMCF-BM beamline which hosts the SAM sample changer. Please visit the Samples & Automounters page in the User Guide for more details about the sample changers and compatible containers for each beamline.

MxLIVE (Mx Laboratory Information Virtual Environment) is the CMCF Laboratory Information Management System that helps your lab organize samples, shipments and experiment information. It serves to integrate your lab with data collection at CMCF beamlines and allows effective use of the sample automounters through the MxDC data collection software. MxLIVE is used in conjunction with MxDC so members of your team can easily check on the progress of experiments taking place at the beamlines and download datasets as they are collected. CMCF Users will notice recent updates to MxLIVE, including streamlined sample information entry that does not rely on spreadsheets, along with new data management options. After logging in, Users will be presented with a brief outline of the new features, which can also be found on the MxLIVE User Guide Page.

CMCF Users have now published 1,000 structures using data collected at the CMCF. There are also 500 peer-reviewed publications acknowledging data collected at the CMCF beamlines. We are pleased to announce that the 1,000th structure is the crystal structure of circumsporozoite protein aTSR domain in complex with 1710 antibody (PDB ID 6B0S, depicted in the image). This structure is part of Jean-Philippe Julien's research into developing a vaccine that prevents the malaria parasite from causing infections. Dr. Julien holds a Canada Research Chair in Structural Immunology and is a scientist in Molecular Medicine at The Hospital for Sick Children Research Institute, as well as assistant professor in the departments of biochemistry and immunology at the University of Toronto.

The 500th paper was the result of research by Mirek Cygler's laboratory at the University of Saskatchewan. Using crystallography as well as other techniques, they now have a better understanding of how iron-sulfur clusters are synthesized in the body. These clusters are key components of many proteins critical to life, and defects in the formation of the clusters can cause severe neurological and metabolic diseases, often with fatal outcomes. The findings were published in Nature Communications [Boniecki, MT; Freibert, SA; Mühlenhoff, U; Lill, R; Cygler, M (2017), Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex,Nature Communications 8(1)] .Dr. Cygler holds a Canada Research Chair in Molecular Medicine Using Synchrotron Light and is a professor in the department of biochemistry at the University of Saskatchewan.

CD22 is a B-cell surface protein involved in regulating the immune response. CD22 knockout mice, for example, have a higher rate of autoimmune disease. CD22's role has been known for some time, but a detailed molecular understanding has been lacking. Now, researchers from the University of Toronto and Hospital for Sick Children (SickKids) have presented a detailed structural model of this key immune component.

Combining X-ray crystallography, SAXS and electron microscopy, the researchers describe the molecular structure of human CD22 alone as well as in complex with a sialyllactose ligand or a therapeutic antibody. Initial crystallographic phasing of a portion of CD22 was accomplished by performing a Hg-MAD experiment on beamline CMCF-BM. The resulting structure allowed solution of the structures of the complexes, for which date were obtained on beamline CMCF-ID. SAXS and electron microscopy data rounded out the picture with the result being a description of the full-length extracellular portion of CD22. The work provides key information about the mechanisms controlling B-cell inhibition and clues for designing new autoimmune therapies. PDB ID 5VKJ

Some bacteria are capable of using a "grappling hook" to move themselves. They extend pili to attach to surfaces and retract them to pull themselves toward the point of attachment. In some cases, these pili are essential for the disease process of virulent bacteria. Using data collected at the CMCF, researchers have characterized the "motor" of one such protein system, known as the Type IVa Pilus (T4aP). X-ray crystal structures allowed researchers to deduce a mechanism whereby ATP binds the core ATPase domains, driving the actions of the pili. PDB ID 5TSG.

We are excited to announce that the new Pilatus3 S 6M detector has been installed and commissioned for use on beamline 08ID-1 beginning in May 2017. To complement the new detector, the computing and storage infrastructure has also been upgraded. One EMC Unity storage server with 40 TB of all flash user space, and three Dell PowerEdge R830 high performance computing nodes with 336 total threads have been installed, all on a new 10 Gbps fibre optic network. For additional information about using the Pilatus detector, please visit the data collection section of our User Guide.

Applications are now open for the 7th Annual CLS Mx Data Collection School. This is an intensive 5-day hands-on data collection school intended to equip participants to effectively collect crystal diffraction data at the synchrotron as well as make use of the CMCF beamlines remotely. Attendance is limited so early application is encouraged. See the School webpage for more information.

CMCF is pleased to announce that a key component of the beamlines upgrade project was delivered this month. The PILATUS3 S Series (6M) detector, which will allow low-noise shutter-less data collection arrived in December. The new detector will be installed on beamline 08ID-1 during the 2017 spring maintenance shutdown, and used for data collection beginning in May 2017. Here, the detector is shown in operation, with the monitor displaying x-rays detected from a test Fe-55 source.

In 1999, the Canadian crystallography community submitted a proposal to the Canadian Light Source (CLS) to build the first crystallography beamline in Canada. This beamline, together with staff and infrastructure, was to be called the Canadian Macromolecular Crystallography Facility (CMCF). In 2005, thanks to the talent and dedication of CLS employees, construction of beamline 08ID-1 was completed. That same year, construction of a second crystallography beamline, 08B1-1, began and was completed in 2009. In 2011, this beamline saw its first remote experiments.

In 2006, ten years ago, the first CMCF experiment was performed. The structure depicted (PDB ID 2i1q) is from the article published with the resulting data (J. Biol. Chem. 281, 39380-7), and represents the structure of RadA recombinase in complex with calcium. This protein plays a critical role in DNA repair.

Since the first CMCF experiment in 2006, the CLS has become a hub of activity for Canadian crystallographers, supporting the work of the majority of the nation’s crystallography laboratories and several international researchers. The number of publications resulting from the work of dedicated researchers using the facility has risen steadily since its inception, with over 425 peer reviewed articles, 800 structures deposited in the Protein Data Bank and several patents and dissertations.

As time advances, so do the needs of the crystallography community. To this end, several exciting upgrades are being implemented. The beamlines’ goals include higher flux on both beamlines, micro-beam capabilities as well as much faster data collection and sample transfer times in order to meet tomorrow’s challenges. The CMCF sincerely thanks all of the dedicated researchers, CLS staff, Beamline Advisory Team and funding agencies for their constant and unwavering support.

The needs of the crystallography community continue to advance. To this end, several exciting upgrades are being implemented at the CMCF with the support of the Beamline Advisory Team. The ultimate goals are higher flux on both beamlines, micro-beam capabilities as well as much faster data collection and sample transfer times in order to meet tomorrow’s new challenges. We are pleased to announce that, as an initial phase, two major components have been approved for beamline 08ID-1.

The first is a PILATUS3 S Series (6M) detector, which will allow low-noise shutter-less data collection. The new detector will be installed during the 2017 spring maintenance shutdown, and used for data collection beginning in May 2017.

The second is an IRELEC ISARA sample changer, which is expected to be ready for operations on beamline 08ID-1 beginning in late fall 2017. The kickoff planning meeting for the new sample changer occurred today. It will enable samples to be changed in under 20 seconds, and expands the range of currently supported bases to include spine pins loaded in standard Uni-pucks.

Installation of components will be performed, as much as possible, during maintenance periods to minimize the impact on User beamtime at the CMCF. Although there will be short periods of time where the beamline is needed for optimization and testing, the impact is expected to be minimal, with beamline 08B1-1 operating continuously during these periods.

This year, scheduled fall maintenance begins October 11. During this time, key components around the CLS and at the beamlines will be inspected and maintained as well as software upgrades implemented and tested. CMCF Users are welcome to submit beamtime requests for beamtime beginning in mid-November. Please see the Schedule for availability.

An intermittent vacuum leak in the double crystal monochromator chambre has been detected on beamline 08ID-1. To prevent any serious problems, the cause will be investigated during the period of March 20 - 27. During this time, beamline 08ID-1 will be in maintenance mode. Beamline 08B1-1 will still be available for experiments. We do not anticipate any negative effects on data collection outside of the planned maintenance period.

Applications are now open for the 6th Annual CLS Mx Data Collection School. This is an intensive 5-day hands-on data collection school intended to equip participants to effectively collect crystal diffraction data at the synchrotron as well as make use of the CMCF beamlines remotely. Additionally, this year's special topic will be an exploration of using the molecular replacement method for structure solution, and making effective use of COOT for model building with invited speaker Dr. Jeffrey Lee. Attendance is limited so early application is encouraged. See the School webpage for more information.

Nonribosomal peptide synthetases (NRPSs) are large, complex proteins responsible for the production of many common antibiotics critical for human health. Making use of the Canadian Macromolecular Crystallography Facility beamlines, researchers have gained a new depth of understanding of NRPSs. Crystal structures of several functional confirmations were determined, supplying critical information about these macromolecular machines. This is an important step if NRPSs are to be used in the production of novel therapeutics. PDB ID: 5es5

The CLS will be in scheduled Maintenance Mode followed by Shutdown Mode until early January 2016. No user beamtime will be available during this short period. Best wishes for a happy and restful holiday season and a prosperous and productive 2016 from everyone at the CMCF!

This year, scheduled fall maintenance will be happening between October 19 - November 30. During this time, no user beamtime will be available. This is a busy time when systems are maintained and components as well as software are upgraded, both around the ring and on individual beamlines. Users may submit CMCF beamtime requests at any time, for beamtime beginning in December.

Regularly-scheduled maintenance of the MAR CCD detectors on both CMCF beamlines has been completed. Beamlines are returning to normal operations. Beamline 08B1-1 will once again be using the MAR 300 HE detector and beamline 08ID-1, the MAR 300 detector.

While the Mar 300HE CCD X-ray detector on beamline 08B1-1 undergoes maintenance, the Mar 225 CCD detector has been temporarily put in place. This will allow the beamline to operate during the detector maintenance. The regular detector is expected to be returned to service this fall.

At this year's Annual Users Meeting, Dr. Michelle (Tonkin) Parker was recognized with the G. Michael Bancroft Ph.D. Thesis Award. Michelle completed her doctoral work, entitled "Molecular Strategies for Active Host Cell Invasion by Apicomplexan Parasites", as a graduate student in Prof. Martin Boulanger's research group at the University of Victoria. During her studies, she published several papers related to the mechanism of malarial infections. New methods to combat malaria have become increasingly important as these parasites develop resistance to available drugs. Through collaborations with groups working on malaria drug and vaccine initiatives, Michelle's results have the potential to aid the development of novel treatment strategies.

Applications are now open for the 5th Annual CLS Mx Data Collection School. This is an intensive 5-day hands-on data collection school intended to equip participants to effectively collect crystal diffraction data at the synchrotron as well as make use of the CMCF beamlines remotely. Additionally, this year's special topic will be an in-depth look at the use of Phenix during structure solution and refinement, with invited speaker Dr. Paul Adams. Attendance is limited so early application is encouraged. See the School webpage for more information.

The Canadian Light Source is celebrating an important milestone in 2015: 10 years of scientific research. This anniversary takes place during the International Year of Light - a celebration of light and light-based research, announced by the United Nations Educational, Scientific and Cultural Organization (UNESCO). The year was designated by the UN to bring awareness to the importance of light and light-based technology, such as synchrotron radiation and its applications. The CLS is planning a series of events; please see the full news release for more information. The International Year of Light follows on the heels of the International Year of Crystallography which occured in 2014.

The microbial community of the human gut, the microbiota, is critical to human nutrition and health. Different diets are associated with different populations of microbiota. A study has appeared in Nature that explores the adaptation of the microbiota to yeast domestication in the human diet. Yeasts have been an important component of the diet for millenia, through such foods as yeast-leavened breads, fermented beverages and such food products as soy sauce. In this detailed study using multiple techniques, including structural data from the CLS, components of yeast (α-mannans) are shown to be an important food source for Bacteroidetes, a dominant member of the microbiota. These specialized bacteria use a mechanism to break down α-mannans by limited cleavage on the surface, generating large oligosaccharides that are subsequently broken down to mannose by periplasmic enzymes, a process that minimizes nutrient loss. PDBID 4c1r.

As 2014 drew to a close, the CMCF celebrated the release of over 500 Protein Data Bank depositions resulting from data collected at the facility. This milestone occured during the International Year of Crystallography and demonstrates the hard work and dedication of CMCF users, the beamline advisory team and the staff of the CLS. As we begin the New Year, CMCF users have now published 300 works containing data obtained from the facility in peer-reviewed journals. Shown: PDBID 2y8s.

The United Nations has proclaimed 2014 the International Year of Crystallography. Looking back through the years, 29 Nobel Prizes have been awarded for discoveries related to crystallography since 1901, an impressive number for any field.

The CLS is excited to celebrate crystallographic achievements of the past and to look to the future in this landmark year.

Applications are now open for the 4th Annual CLS Mx Data Collection School! This is an intensive 5-day hands-on data collection school intended to equip participants for effective crystal diffraction data collection, both on site and using CMCF beamlines remotely. This year, participants will delve into special topics including the molecular replacement technique, making effective use of COOT as well as structure validation with invited speaker Dr. Trevor Moraes. Attendance is limited so early application is encouraged. See the School webpage for more information.

It is again time for December maintenance and the holiday season. All of the CLS will be in scheduled Maintenance Mode followed by Shutdown Mode until January 2014. No user beamtime will be available during this short period. Best wishes for a happy and restful holiday season and a prosperous and productive 2014 from everyone at the CMCF!

It is once again time for fall maintenance and all of the CLS will be in scheduled Maintenance Mode until mid-November. No User beamtime will be available during this short period. This is a busy time when systems are maintained and components as well as software are upgraded, both around the ring and on individual beamlines. Users may submit CMCF beamtime requests for the mid-November to December period.

RNA (ribonucleic acid) sequences, although usually single-stranded, can sometimes form double-helical structures. Long RNA sequences having repeating adenine residues, poly(rA), are present on messenger RNA (mRNA), which is transcribed from DNA as a step toward the production of proteins. Poly(rA) RNA was predicted to have the ability to form a double-helix in 1961 based on fibre diffraction experiments. Its detailed structure has only been confirmed by X-ray crystallography recently. Researchers at McGill University have crystallized (rA)11 RNA sequences and combined data collected at the Canadian Light Source and the Cornell High Energy Synchrotron Source to obtain a very detailed 1.0 Å resolution crystal structure of this double-helix. The structure, obtained at physiological pH, shows a parallel double-helix. Ammonium ions stabilize the structure by binding to RNA phosphate groups and adenine N1 atoms, while N7 positions are engaged in hydrogen bonding. Contrary to antiparallel DNA, the poly(rA) double helix shows no major or minor grooves, but rather grooves of equal size. The extent of poly(rA) RNA double-helix formation in mRNA and in other systems remains to be discovered. Researchers believe the structure may be physiologically important, especially under conditions where there is a high local concentration of poly(rA). This can happen, for instance, under conditions where cells are stressed and mRNA become concentrated in RNA granules within cells. PDB ID: 4jrd.

The Canadian Macromolecular Crystallography Facility (CMCF) is excited to announce that the first session of Remote data collection on beamline 08ID-1 occurred this week on May 23. Dr. Wolfram Tempel and colleagues from the Structural Genomics Consortium (SGC) in Toronto were the first to put the Remote Control capabilities of this highly-productive Canadian Light Source crystallography beamline to the test. This mode of operation allows researchers to collect data as though they were present at the beamline without leaving their home laboratories, thereby saving costs associated with travel and making data collection extremely efficient. The researchers shipped their samples in standard containers which were loaded into the robotic automounter by beamline staff. Using a freely-available software client installed on their laboratory computers, the research team was able to connect to the beamline through a secure encrypted channel in order to perform their experiments with minimal intervention by staff. This new capability follows on the heels of beamline 08B1-1, which has had Remote Control capabilities in place since 2011. Remote Control is now available on both CMCF beamlines to Users with active proposals, after completing appropriate training. Users wishing to use this capability should contact beamline staff to discuss their project.

Applications are now open for the 3rd Annual CLS Mx Data Collection School. This is an intensive 5-day hands-on data collection school intended to equip participants to effectively collect crystal diffraction data at the synchrotron as well as make use of the CMCF beamlines remotely. Additionally, this year's special topic will be an in-depth look at the use of Phenix during structure solution and refinement, with invited speaker Dr. Paul Adams. Attendance is limited so early application is encouraged. See the School webpage for more information.

During viral infections with viruses such as the flu virus, RNAs having 5'-triphosphate groups (PPP-RNAs) are produced which do not have the usual eukaryotic 5'-cap. A recently-discovered protein, IFIT, can bind this foreign RNA, allowing the immune system to distinguish "self" from "non-self" RNA and initiate processes that serve to prevent the virus from making viable copies of itself. The mechanism for IFIT recognition of foreign viral RNA is the subject of new research, which may pave the way for new developments in the treatment of viral infections. Researchers have used data collected at the CMCF to solve crystal structures of a human IFIT with and without bound PPP-RNAs. These fascinating structures reveal a cavity within the protein designed to accept only single-stranded PPP-RNAs, yet with the necessary ability to be non sequence specific. PDB ID: 4hoq

Due to recent construction and rearrangement of roadways on the university campus, the Canadian Light Source has received a new street address and postal code. Our new address is:Canadian Macromolecular Crystallography FacilityCanadian Light Source, Inc.University of Saskatchewan44 Innovation BoulevardSaskatoon, SKCanada S7N 2V3

β-lactams are an important class of antibiotics that includes penicillins and carbapenems. A readily-transferable antibiotic resistance factor called New Delhi metallo-β-lactamase-1 (NDM-1) has been found in enteric bacteria. It confers resistance to β-lactams including some critical antibiotics that are presently considered to be the "last line of defence" against multi-drug resistant Gram negative bacteria. The most clinically significant of these lactamases have 2 active site Zn ions. Researchers have used data collected at the CMCF to describe the details of how β-lactam antibiotics are recognized by these Zn-containing enzymes, including a crystal structure having a potential inhibitor bound.

Small RNA molecules that occur naturally in animals and plants are critical for the regulation of eukaryotic cellular processes. They serve to silence gene expression in various ways including via chromosomal modifications and post-transcriptional effects. These small RNAs are typically 20-30 nucleotides in length and associate with Argonaute proteins to form the RNA-induced silencing complex. In order to function properly, the Argonaute protein must bind to the correct class of small RNA. The 5'-nucleotide of the small RNA is recognized by the MID domain in human Argonaute proteins and this is critical for the correct sorting and association. Now researchers have determined that a similar structural mechanism also occurs in plant Argonaute proteins and, because of the greater complexity of small RNAs in plants, recognition interactions appear to have a corresponding complexity all their own. PDB ID: 4g0x.

Properly-functioning voltage-gated sodium channels are critical to the normal contraction and relaxation of heart muscle cells. Calcium ions bound to another protein called calmodulin can modulate these channels. Researchers have used data obtained at the CMCF to solve the 1.35 Å structure of calcium-bound calmodulin in complex with the inactivation gate of a sodium channel. Several mutations near the calmodulin binding site have been identified which result in arrhythmias or other physiological problems. View the full CLS press release here.

Applications are now open for the 2nd Annual CLS Mx Data Collection School. This is an intensive 5-day hands-on data collection school intended to equip participants to effectively collect crystal diffraction data at the synchrotron as well as make use of the CMCF beamlines remotely. Additionally, this year's special topic will be an in-depth look at the use of COOT during structure solution and modeling, with invited speaker Dr. Trevor Moraes. Attendance is limited so early application is encouraged. See the School webpage for more information.

It is once again time for December maintenance and the holiday season. All of the CLS will be in scheduled Maintenance Mode followed by Shut Down Mode until January 2012. No user beamtime will be available during this short period. Best wishes for a happy and restful holiday season and a prosperous and productive 2012 from everyone at the CMCF!

It is once again time for fall maintenance and all of the CLS will be in scheduled Maintenance Mode until mid-November. No user beamtime will be available during this short period. This is a busy time when critical systems are maintained and components are upgraded, both in the ring and on individual beamlines.

Toxoplasma and Plasmodium parasites cause numerous diseases worldwide, including malaria and toxoplasmosis. Interestingly, these parasites attack host cells in a very active manner, providing the receptor for binding to the host cell. Interaction thus occurs through a protein called AMA1 to a rhoptry neck (RON) complex provided by the parasite and injected into the host cell. Now researchers have used data collected at the CMCF to determined the structure of AMA1 with a RON2 peptide to give insight into this interaction. PDB ID: 2Y8T and 2Y8S.

Bacteria from the genus Chlamydia cause a number of serious health conditions in humans. As antibiotic resistance increases in these organisms, methods of combating infections are becomming increasingly urgent. Researchers from the University of Alberta are using the Canadian Macromolecular Crystallography Facility in their investigation of an alternate route of lysine biosynthesis in Chlamydia that is an excellent target for the development of new and specific antibiotics.

The miniKappa goniometer head has been installed on beamline 08B1-1. Previously, rotation was only possible about the omega-axis during data collection. Additional orientations for crystals are now possible with the miniKappa axis. This is especially useful for samples having smaller unit cells or where precise orientation of the crystal axes is important. Users can control this axis through the MXDC data collection software's Beamline Setup tab. Note that beamline 08ID-1 remains in the traditional configuration with rotation about the omega-axis only.

MxLIVE (Mx Laboratory Information Virtual Environment) is the CMCF Laboratory Information Management System that will help your lab organize samples, shipments and experimental information to integrate your lab with data collection at the beamlines. When MxLIVE is used in conjunction with the MxDC data collection software, members of your team not at the beamline can easily check on the progress of experiments taking place at the beamlines and even view diffraction images through a secure web server. MxLIVE also helps you organize all of your crystal samples, information about their properties and contents, experimental parameters that you want to use for data collection, screening results and experimental results! An invaluable tool whether you are collecting data at the beamlines, collecting data remotely or sending samples for Mail-In data collection. For more information visit the MxLIVE page.

Researchers from Dr. Emil Pai's laboratory at the Ontario Cancer Institute were the first to benefit from the remote control capabilities that recently became available on beamline 08B1-1. This mode of operation allows researchers to collect data as though they were present at the beamline without leaving their home laboratories, thereby saving costs associated with travel. The researchers shipped their samples in standard containers which were loaded into the robotic automounter by beamline staff. Using a freely-available software client installed on their laboratory computers, the research team was able to connect to the beamline through a secure encrypted channel in order to perform their experiments with minimal intervention by beamline staff. Remote control is available on beamline 08B1-1 to users with an active proposal after completing appropriate training. Users wishing to use this capability should contact beamline staff.

The application deadline for the 1st Annual CLS Mx Data Collection School has been extended by one week to March 8, 2011. This is an intensive 5-day hands-on data collection school intended to equip participants to effectively collect crystal diffraction data at the synchrotron as well as make use of the CMCF beamlines remotely. Additionally, this year's special topic will be an in-depth look at the use of PHENIX for data analysis and structure solution with invited speaker Dr. Paul Adams. The school will take place May 16 - 20, 2011. Attendance is limited. See the School webpage for more information.

Chaperone proteins make possible the correct folding of other protein molecules in the cell. Researchers have induced bacteria to overproduce a periplasmic chaperone protein called Spy. These unique cradle-shaped dimers help protein refolding and suppress protein aggregation independently of ATP.

The 08ID-1 endstation has been upgraded and includes an on-axis visualization system and mini-beam apparatus. For standard use, the 100 micron beam size has an approximate flux of 2E12 photons per second. In January, characterization will proceed with smaller 50 micron, and eventually 20 micron beam sizes. The beamline is now available to users. Automounter testing with the new endstation is progressing well but the automounter is not yet available for general users. For now, users who wish to use an automounter may contact staff about using the beamline 08B1-1 automounter. For further details, more images and instructions about collecting data with the new 08ID-1 endstation, please visit the following website.

Applications are now open for the 1st Annual CLS Mx Data Collection School. This is an intensive 5-day hands-on data collection school intended to equip participants to effectively collect crystal diffraction data at the synchrotron as well as make use of the CMCF beamlines remotely. Additionally, this year's special topic will be an in-depth look at the use of PHENIX for data analysis and structure solution with invited speaker Dr. Paul Adams. Attendance is limited so early application is encouraged. See the School webpage for more information.

Genetic variation in ryanodine receptor 'hotspots' can play a role in diseases affecting muscles, including congenital heart disease. Researchers from the University of British Columbia have combined crystallographic data obtained at beamline 08ID-1 and the Stanford Synchrotron Radiation Lightsource with electron microscopy data to shed light on amino-terminal ryanodine receptor disease hotspot. To view the complete media release click here. PDB ID: 2XOA.

HMG/CHA aldolase from Pseudomonas putida is part of a larger pathway for breaking down harmful components of fossil fuel pollution and coal derivatives (fluorene and its analogues) and substances found in plastics and pesticides (phthalate isomers). The researchers have grown crystals of the enzyme and solved the crystal structure in order to better understand how the active site is organized. This has allowed them to propose a catalytic mechanism based on the structural features, kinetics and information available about related aldolases. PDB ID: 3NOJ.

We are pleased to announce that the installation and testing of the automounter on beamline 08B1-1 has been completed and that it is now available for users. Please contact beamline staff to make arrangements for using the automounter and for additional information.

The hydration level of your crystals can have an impact on their diffraction quality. The HC1 humidity control device is now available for use at beamline 08B1-1. The instrument allows you to control the relative humidity surrounding a mounted crystal through the delivery of a precisely callibrated air stream. If you are interested in using the HC1, please discuss your experiment with beamline staff. For more information on the device and its possible applications,please visit the User Guide.

The need for novel antibiotics is increasingly pressing in the face of the rising threat of bacteria resistant to existing drugs. One approach for such antibiotics is to target the building blocks of bacterial cell walls. One such component is lipopolysaccharide, formed from sugars that are in turn produced using the enzyme UDP-galactopyranose mutase (UGM). Researchers from the University of Saskatchewan isolated UGM in a form bound to sugars and obtained its crystal structure. This information may be used to design drugs that inhibit the enzyme's activity and thus block the formation of bacterial cell walls.

Diatoms are unicellular phytoplankton that account for much of the primary productivity in the world's oceans. The growth and population size of diatoms is dependent on the availability of iron. Using data from the 08ID-1 beamline, researchers from the University of British Columbia determined that pennate diatoms are able to produce an iron-concentrating protein, ferritin, to store iron and thrive in areas that are usually iron-poor.

Mycobacterium tuberculosis (Mtb), the bacteria that causes tuberculosis, is a resilient organism that can only be effectively treated by a lengthy course of multiple drugs. Mtb is able to survive by harvesting the cholesterol stored in white blood cells. Researchers from the University of British Columbia used the 08ID-1 beamline to collect data about the strucuture of KshAB, one of the enzymes used to break down cholesterol. This structural information can be used to design drugs to interfere with the enzyme and develop improved drugs for the treatment of tuberculosis.

Malaria, caused by Plasmodia parasites, has re-emerged as a major problem, imposing its fatal effects on human health, especially due to multidrug resistance. In Plasmodia, orotidine 5’-monophosphate decarboxylase (ODCase) is an essential enzyme for the de novo synthesis of uridine 5’-monophosphate. Impairing ODCase in these pathogens is a promising strategy to develop novel classes of therapeutics. Researchers from the group of Dr. E. Pai (University of Toronto) used data from the 08ID-1 beamline to investigate the structure–activity relationships of various novel inhibitors of ODCase.

Outbreaks of Norwalk virus are notorious for causing severe dehydration due to vomiting and diarrhea. The currently untreatable bug belongs to a superfamily of viruses that stores their genetic code as RNA. Researchers at the University of Calgary used high-resolution data from the 08ID-1 beamline to determine the structure the Norwalk virus polymerase in various complexed states. The information is crucial to better understand viral replication and for drug development.

Xenon is a noble gas, which binds to specific sites in a biological macromolecule and can therefore be used to form heavy atom derivatives for structure determination. The Xenon Chamber is a simple yet effective device designed to pressurize loop-mounted biological macromolecular crystals in the presence of xenon gas at room temperature. Crystals mounted in loops such as the CrystalCap system are placed into the Xenon Chamber. Once sealed, the chamber is pressurized with xenon gas so that the crystal and macromolecules are equilibrated in a vapor saturated xenon atmosphere. Following depressurization of the chamber, the loop-mounted crystal is simply lifted and slid along the Xenon Chamber track and quickly lowered into a dewar for freezing in liquid nitrogen or propane.

Users wishing to operate this equipment should contact the beamline staff for operating instructions and training.